High Aldosterone To Renin Ratio Research Articles

Predictors of successful outcome after adrenalectomy for unilateral primary aldosteronism.

Unilateral primary aldosteronism (UPA) is the most frequent surgically curable form of endocrine hypertension. Adrenalectomy is the cornerstone of treatment for UPA, but outcomes after surgery are variable. The cause of resistant hypertension after surgery is still a matter of debate. Our aim was to investigate cure rates after surgery and to evaluate preoperative factors that might influence the surgical outcome. Between 2000 and 2021, the charts of 71 Tunisian patients who underwent laparoscopic adrenalectomy for UPA were retrospectively reviewed. Preoperative medical records were collected and follow-up data (1-158 months) were registered. Antihypertensive medication doses were calculated using defined daily doses (DDD) and postoperative outcomes were assessed using the Primary Aldosteronism Surgical Outcome (PASO) criterion. Of 91 enrolled patients, 71 (59% women, mean age 46 years, median length of follow-up 21 months) were suitable for evaluation. Thirty-four patients (48%) had complete clinical success according to the PASO criteria. The most relevant factors associated with complete clinical success on univariate analysis were: absence of diabetes (p= 0.007), low body mass index (BMI) (p= 0.001), lower preoperative DDD (p= 0.01), preoperatively controlled blood pressure (p= 0.024), higher plasma aldosterone to renin ratio (ARR) (p= 0.001), adenoma subtyping (p <0.001) and aldosteronoma resolution score (ARS) (p= 0.002). Multivariate regression analysis showed that the major predictors of complete clinical success were absence of diabetes (OR: 5.205), a BMI < 30 (OR: 4.930), a plasma ARR > 332 (OR: 4.554) and an ARS ≥ 3 (OR: 2.056). Complete and partial clinical response rates were achieved in respectively 48 and 43% of cases. The main predictors of complete resolution of hypertension were absence of diabetes, low BMI, high plasma ARR and high ARS. Taking these factors into account may help identify patients at risk of persistent postoperative hypertension who may require long-term surveillance and medication.

Should Adrenal Venous Sampling Be Performed in PA Patients Without Apparent Adrenal Tumors?

IntroductionSome aldosterone-producing micro-adenomas cannot be detected through image inspection. Therefore, adrenal venous sampling (AVS) is often performed, even in primary aldosteronism (PA) patients who have no apparent adrenal tumors (ATs) on imaging. In most of these cases, however, the PA is bilateral.ObjectiveTo clarify the clinical need for AVS in PA patients without apparent ATs, taking into consideration the rates of adrenalectomy.MethodsThis is a retrospective cross-sectional study assessing 1586 PA patients without apparent ATs in the multicenter Japan PA study (JPAS). We analyzed which parameters could be used to distinguish unilateral PA patients without apparent ATs from bilateral patients. We also analyzed the prevalences of adrenalectomy in unilateral PA patients.ResultsThe unilateral subtype without an apparent AT was diagnosed in 200 (12.6%) of 1586 PA patients. Being young and female with a short hypertension duration, normokalemia, low creatinine level, low plasma aldosterone concentration, and low aldosterone-to-renin ratio (ARR) was significantly more common in bilateral than unilateral PA patients. If PA patients without apparent ATs were female and normokalemic with a low ARR (<560 pg/ml per ng/ml/h), the rate of unilateral PA was only 5 (1.1%) out of 444. Moreover, 77 (38.5%) of the 200 did not receive adrenalectomy, despite being diagnosed with the unilateral subtype based on AVS.ConclusionThe low prevalence of the unilateral subtype in PA patients without apparent ATs suggests AVS is not indicated for all of these patients. AVS could be skipped in female normokalemic PA patients without apparent ATs if their ARRs are not high. However, AVS should be considered for male hypokalemic PA patients with high ARRs because the rates of the unilateral subtype are high in these patients.

Plasma renin activity, serum aldosterone concentration and selected organ damage indices in essential arterial hypertension.

IntroductionThe aim of this study was to assess the relations between plasma renin activity (PRA), serum aldosterone concentration (ALDO) and selected asymptomatic organ damage (AOD) indices in mild primary arterial hypertension (AH).Material and methodsWe measured PRA, ALDO, and selected AOD indices (carotid-femoral pulse wave velocity (cfPWV), central aortic pulse pressure (cPP), estimated glomerular filtration rate (eGFR)) in 122 patients with untreated AH.ResultsPatients with high PRA (≥ 0.65 ng/ml/h) were characterized by lower plasma sodium and aldosterone to renin ratio (ARR), higher ALDO, but a similar level of AOD indices compared to patients with low PRA. cfPWV (p = 0.04) and cPP (p = 0.019) increased with ARR, while eGFR decreased with ALDO (p = 0.008). Only eGFR was independently correlated with ALDO. In subjects with simultaneously high PRA and ARR values, we found significantly higher cfPWV (p = 0.02) and cPP (p = 0.04) and lower eGFR (p = 0.02) than in those with high PRA but low ARR values.ConclusionsAssessment of the influence of the renin-angiotensin-aldosterone system (RAAS) on AOD should include the relationship between renin and aldosterone. The PRA itself has no predictive value for AOD. More advanced arterial stiffness and renal impairment are associated with increased PRA and ARR. The RAAS activity might be useful in AOD prediction and hypertension severity assessment.

Relation of the renin–angiotensin–aldosterone system with potential cardiac injury and remodelling: the SABPA study

Purpose: The renin-angiotensin-aldosterone system (RAAS) plays an important role in maintaining hemodynamic homeostasis. Ethnic disparities exist regarding RAAS activity due to sympathetic activity and sodium-water retention, however the implications thereof on cardiac damage is unknown. This study investigated the associations of cardiac troponin T (cTnT), N-terminal pro-brain natriuretic peptide (NTproBNP) and subclinical LVH with components of the RAAS (renin, aldosterone and aldosterone-to-renin ratio (ARR)) and copeptin in a black and white South African cohort.Materials and methods: The study population consisted of 305 participants (black = 139, white = 166) aged 20–62 years. Serum cTnT, NTproBNP, Cornell product, components of the RAAS (active renin, aldosterone and ARR) and copeptin were determined.Results: The black group had lower renin (p < 0.001) and higher ARR (p < 0.001), cTnT (p = 0.015) and Cornell product compared to whites (all p < 0.001). NTproBNP and copeptin were similar between the groups. After forward stepwise adjustments for multiple confounders, inverse associations of cTnT with renin (β = −0.17, p = 0.018) and aldosterone (β = −0.14, p = 0.048) as well as an inverse association between NTproBNP and aldosterone (β = −0.25, p < 0.001) were observed in the white population only. In the black group cTnT associated positively with renin (β = 0.16, p = 0.040) and copeptin (β = 0.21, p = 0.020) and inversely with ARR (β = −0.15, p = 0.047). Additionally, NTproBNP associated positively with copeptin (β = 0.18, p = 0.045). No correlations were observed between the RAAS and Cornell product in any of the groups.Conclusions: Our findings suggest that RAAS, together with cardiac stress may function differently in cardiac damage and remodelling in the two ethnic groups; which may influence treatment in clinical practice.

RENIN, ALDOSTERONE, THE ALDOSTERONE-TO-RENIN RATIO AND INCIDENT ARTERIAL HYPERTENSION AMONG NORMOTENSIVE SUBJECTS FROM THE POPULATION

Objective: To investigate the predictive value of directly-measured plasma renin concentration (PRC), aldosterone (PAC) and the aldosterone-to-renin ratio (ARR) for incident arterial hypertension in the population. Design and method: From the sample of 15,010 participants of the population-based Gutenberg Health Study, only normotensive subjects at baseline (n = 5,362) were included in the present analysis. Concentrations of renin and aldosterone were determined by a competitive chemiluminescence immunoassay (CLIA) using the fully-automated LIAISON® platform (DiaSorin). Extreme quartiles (Q) of biomarker concentrations were compared by means of regression analysis, adjusted for traditional CVRF, renal function and hormonal status (in women only). Results: During a follow-up period of five years, new-onset hypertension developed in 996 participants (18.6%). Among men, the relative risk (RR) for incident arterial hypertension was found to be 1.49 (95% confidence interval (CI) 1.19–1.86; p = 0.00054; Q1 vs Q4ref) for renin; 1.26 (95%CI 1.02–1.56, p = 0.029; Q4 vs Q1ref) for aldosterone and 1.70 (95%CI 1.33–2.12; p < 0.0001; Q4 vs Q1ref) for ARR in a fully adjusted model. In females, only high ARR was an independent predictor of incident arterial hypertension (RR 1.29 (95% CI 1.04–1.62); p = 0.024). In the subgroup of individuals with concentrations within the reference range, only ARR (Q4 vs Q1ref) was predictive for the new-onset hypertension in men (RR 1.44 (95%CI 1.13–1.83) p = 0.003). Synergistic effects of co-prevalent obesity and biomarker concentrations on incident hypertension were also demonstrated, resulting in a markedly higher risk estimates (e.g. men in Q4 of ARR and having BMI >= 30 kg/m2 had compared to subjects with normal weight and low ARR (Q1ref), a RR of 2.92 (95% 1.90–4.49); p < 0.0001)). Conclusions: Among normotensives from the general population ARR possesses a stronger predictive value for the development of new-onset hypertension than renin or aldosterone alone. The prediction of the development of arterial hypertension by ARR was even stronger in obese subjects.

SAT-060 Analysis of over 24,000 Aldosterone to Renin Ratio for Screening Hypertensive Patients for Primary Aldosteronism

Primary aldosteronism remains an underdiagnosed and undertreated endocrine disease2. More than 100 million adults in the USA are hypertensive, and 5% or more of the cases may be related to primary aldosteronism. The value of primary aldosteronism diagnosis is to guide surgical or medical treatment. Aldosterone to Renin Ratio (ARR) is the screening tool designated by the Endocrine Society’s 2016 guideline1 aimed at screening hypertensive patients for primary aldosteronism. Used properly, the test has a high negative predictive value and a moderate positive predictive value2. 24,508 ARR results were surveyed to determine the positivity rate for the ARR screen. Various cancellations eliminated 1592 results, and 20,656 results were valid. The frequency of ARR results greater than 30 was 8.75%. In addition, another 1.11% of results had undetectable renin values with aldosterone values greater than 20 ng/dL, thus these were designated as screen positives. The total frequency of screen positivity was 9.86%. A secondary study goal was to investigate available characteristics of the ARR positive screen patients. The median age of the positive ARR screen patients (57) was not significantly different from the age of all patients screened (56). The percent female was only slightly lower in the positive ARR group than in the negatives (57% vs 54%). High ARR patients had low potassium -with a frequency of 11.5%. The most common ICD10 codes in the screen positive patients were for primary hypertension (20.9% of all samples but 52.9% of positives), followed by hypokalemia (3.7% of all samples but 9.5% of positives), disorder of the adrenal gland (1.8% of all samples but 4.6% of positives). Chronic kidney disease due to hypertension was also found more frequently in positive ARR patients. In addition, many other codes at less than 1%, including vitamin D deficiency, hyperlipidemia, and hypothyroidism were found less frequently in ARR positive than in negative patients. Conclusions: The ratio of two routine blood tests, aldosterone to renin may have large implications for the hypertensive patient because high blood pressure due to primary aldosteronism may be better controlled medically or surgically with appropriate diagnosis. The positive screen rate in a large series of patient screens was about 10%. The Medicare cost of ARR screening is less than $80.00, and the reasonable cost underscores cost-effective ARR test utilization for screening hypertensive patients.

Evaluation of Biochemical Conditions Allowing Bypass of Confirmatory Testing in The Workup of Primary Aldosteronism: A Retrospective Study in a French Hypertensive Population.

The diagnostic workup for primary aldosteronism includes a screening step using the aldosterone-to-renin ratio (ARR) and a confirmatory step based on dynamic testing of aldosterone secretion autonomy. International guidelines suggest that precise clinical and biochemical conditions may allow the bypassing of the confirmatory step, however, data which validate hormone thresholds defining such conditions are lacking. At our tertiary center, we retrospectively examined a cohort of 173 hypertensive patients screened for PA by the ARR, of whom 120 had positive screening and passed a saline infusion test (SIT) or a captopril challenge test (CCT). Fifty-nine had PA, including 34 Conn adenomas and 25 with idiopathic aldosteronism (IA). Using a threshold of 160 pmol/l, post-SIT plasma aldosterone concentration (PAC) identified PA with 86.4% sensitivity, 94.7% specificity, and a negative predictive value of 92.3%. Of those subjects with a high ARR and a PAC above 550 pmol/l, 93% had a positive SIT, while 100% of subjects with a high ARR, but a PAC under 240 pmol/l had a negative SIT. Our results thus validate the biochemical conditions defined in the French and US guidelines for bypassing the confirmatory step in the workup for PA diagnosis.

Change in kidney function after unilateral adrenalectomy in patients with primary aldosteronism: identification of risk factors for decreased kidney function.

Glomerular filtration rate (GFR) has been reported to decrease after unilateral adrenalectomy in patients with primary aldosteronism (PA). The aim of this study was to identify clinical predictors for decreased GFR after adrenalectomy in patients with PA. The records of 187 patients (98 patients with PA and 89 with non-PA adrenal disease) who were followed up for at least 6months after unilateral adrenalectomy were retrospectively analyzed. Estimated GFR (eGFR) was investigated at 1, 3, and 6months postoperatively. Preoperative risk factors for eGFR% decline at 1month ([preoperative eGFR-eGFR at 1month]/preoperative eGFR × 100) and postoperative CKD development were investigated. The eGFR decreased significantly at 1month and remained stable in the PA group. However, there were no significant changes in eGFR in the non-PA group over the 6-month period. In the PA group, a high preoperative eGFR and high aldosterone to renin ratio (ARR) were independently associated with eGFR% decline at 1month. In patients with PA but without preoperative CKD (n = 68), a low preoperative eGFR and high ARR were independent risk factors for developing postoperative CKD. The best preoperative cut-off values of eGFR and ARR for predicting the development of postoperative CKD were ≤ 102ml/min/1.73m2 and ≥ 448ng/dl:ng/ml/h, respectively. Renal function deteriorated significantly after unilateral adrenalectomy in patients with PA. Clinicians must pay attention to postoperative renal function in PA patients at elevated risk of developing decreased kidney function.

PP.07.16] RELATIONSHIP BETWEEN PLASMA RENIN ACTIVITY, PLASMA ALDOSTERONE AND SELECTED ASYMPTOMATIC ORGAN DAMAGE INDICES IN ESSENTIAL ARTERIAL HYPERTENSION

Objective: To assess the relationship between plasma renin activity (PRA), serum aldosterone concentration (ALDO) and selected asymptomatic organ damage (AOD) indices in mild primary arterial hypertension (AH).Design and method: In 122 patients (61 men and 61 women) with untreated essential AH stage 1 (140/90 > BP < 160/100 mm Hg) and age 30–75 years we measured PRA, ALDO, and selected AOD indices (left ventricular mass index, carotid artery intima media thickness, carotid-femoral pulse wave velocity (cfPWV), central aortic pulse pressure (cPP), estimated glomerular filtration rate (eGFR)). Although the study group included only patients with mild essential AH without typical indications to perform screening for primary aldosteronism we decided to exclude patients with an aldosterone-to-renin ratio (ARR) >100 ng/dl/ng/ml/h and aldosterone concentration >15 ng/dl. Results: Based on PRA results, patients were divided into two subgroups, “low-renin” and “high-renin”, according to the Laragh and Alderman criteria (low-renin: PRA < 0.65 ng/ml/h, high-renin: PRA > 0.65 ng/ml/h). Patients with high PRA (>0.65 ng/ml/h) were characterized by lower plasma sodium concentration, several times lower aldosterone-to-renin ratio (ARR), higher ALDO, but similar level of AOD indices compared to patients with low PRA. Among AOD indices, cfPWV (p = 0.04) and cPP (p = 0.019) increased with ARR, while eGFR decreased with ALDO (p = 0.008). After adjusting for age, sex, and BMI, only eGFR was significantly correlated with ALDO (Table 1). In subjects with simultaneously high PRA and ARR values, we found significantly higher cfPWV (p = 0.02) and cPP (p = 0.04) and lower eGFR (p = 0.02) than in those with high PRA but low ARR values. Conclusions: In mild hypertension, assessment of RAAS influence on AOD should include the reciprocal relationship between renin and aldosterone. PRA itself has no predictive value for AOD. More advanced arterial stiffness and renal impairment are associated with increased PRA and ARR. RAAS activity might be useful in AOD prediction and hypertension severity assessment.

Magnitude of Resistant Hypertension and Impact of Aldosterone to Renin Ratio In Resistant Hypertension

Background: Resistant hypertension is a common clinical problem faced by both primary care clinicians and specialist. The magnitude of resistant hypertension is highly variable and is reported to be in the range of 12.8% to 25%. Increased incidences of elevated aldosterone levels have been implicated in difficult to manage hypertension. Aim: To estimate the magnitude and identifiable causes of resistant hypertension among on therapy hypertensive patients, and also to compare the aldosterone levels and aldoster one ren in ratio between resistant and controlled hypertensive conditions. Subjects and Methods: This Multistage, exploratory comparative study was conducted at JSS Hospital and Research Centre, Mysore, India for two years. 1537 adult hypertensive on antihypertensive drugs for a minimum of six months were included. Those who were on three or more antihypertensive medication with blood pressure not under control were defined as having resistant hypertension. Results: Prevalence of resistant hypertension was 16.13% (n=248). There was a marginal difference in the prevalence of resistant hypertension in male (51.2%, n=127) and females (48.8%, n=121). Renal diseases were the most common cause of resistant hypertension (n=103). Aldosterone Rennin Ratio >20 was significantly higher in resistant hypertensives without evident secondary cause compared to hypertensive’s who were well controlled with less than three antihypertensive. Conclusion: Frequency of hyperal dosteronism with high ARR (Aldosterone to Renin Ratio) among resistant hypertensive’s with no evident secondary cause for hypertension, probably suggestive of Primary hyperal dosteronism. This makes us to consider estimation of ARR in resistant hypertensive and also consider use of aldosterone antagonists as primary option for good control of Hypertension. Key words: Resistant Hypertension, Renin, Aldoster one, Aldoster one renin ratio, Primary hyperal dosteronism.

Evaluation of the (1-24) adrenocorticotropin stimulation test for the diagnosis of primary aldosteronism.

Objective:The purpose of this study was to investigate the diagnostic power of the adrenocorticotropin (ACTH) stimulation test in patients with primary aldosteronism (PA) and those with aldosterone-producing adenoma (APA).Design:This study was based on a retrospective database analysis.Subjects and methods:We assessed 158 hypertensive patients with a high plasma aldosterone-to-renin ratio (ARR) including 97 with at least one positive confirmatory test result who did not undergo surgery and comprised a “possible PA” group, 19 with negative results in all tests who were the “non-PA” group, and 41 diagnosed with APA following surgery who were the APA group. The “confirmed PA group” included APA patients and patients from the possible PA group showing both high ARR and hypokalemia. One case was diagnosed as a metastasis.Results:Receiver-operating characteristic (ROC) analysis showed that the diagnostic accuracy of ACTH test was not very effective in differentiating between APA patients and possible PA and non-PA patients. The optimal cut-off value of maximal plasma aldosterone concentration for differentiating between patient in the confirmed PA group and other patients showed moderate accuracy.Conclusions:The ACTH test may not be useful as a screening or confirmatory test, but the test may be useful for differentiating between patients with confirmed PA and the rest of the cohort. The positive finding of the ACTH test may at least support a higher likelihood of lateralizing on adrenal venous sampling.

Abstract 14714: Association of Plasma Renin and Aldosterone Levels With Future Left Ventricular Structure and Function: The Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: The renin-angiotensin-aldosterone-system (RAAS) has been implicated in left ventricular (LV) hypertrophy and dysfunction. We explore the association of circulating levels of plasma renin activity (PRA) and aldosterone to subclinical measures of LV structure and function from MRI. Methods: The MESA study enrolled 6814 participants free of cardiovascular disease at baseline (2000-2002). We included MESA participants who had blood assayed for measurement of PRA and aldosterone levels at the second/third follow-up exams (2003-2005) and underwent MRI at the fifth follow-up exam (2010 -2012). We excluded participants on hypertension medication (N=509). Harmonic phase analysis was used to compute circumferential strain and torsion from tagged MRI; LV function and structure measures were obtained from cine images. Linear regression evaluated the relationship between PRA, aldosterone and aldosterone to renin ratio (ARR) with LV structure and function. The models included adjustments for cardiovascular risk factors and demographics at the time of assays (model 1) and at the time of imaging (model 2) separately. Results: At the time of assays, the participants (N=384) were 59±8 years, 53% male, 43% Caucasian, 13% African-American, 17% Chinese, 28% Hispanic, 4% diabetic, with median levels of PRA 0.56 ng/ml (IQR:0.30-0.97), aldosterone 126 pg/ml (IQR:90-176) and ARR 120 ng/ml to pg/ml (IQR:53-234). Higher PRA was associated with lower LV end-diastolic volume index. Higher PRA was associated with higher mass-volume ratio and torsion. Higher ARR was associated with higher LV volume and lower torsion. Conclusions: In individuals not on hypertension medications, higher PRA was associated with concentric remodeling and higher torsion 7 years later but not to LV function. Also, higher ARR was associated with eccentric LV chamber remodeling and lower torsion. In conclusion, RAAS activity may be implicated in future concentric/eccentric LV remodeling.

Unadjusted Plasma Renin Activity as a "First-Look" Test to Decide Upon Further Investigations for Primary Aldosteronism.

The authors sought to define the 95th percentile of plasma renin activity (PRA) in a sample of patients with confirmed primary aldosteronism (PA) prior to adjustment of medications as a practical "first-look" test to identify those with very low ultimate likelihood of having PA. The aldosterone to renin ratio (ARR) was measured without adjustment of antihypertensive medications, with further workup as appropriate. Two groups were defined: patients with surgically "confirmed PA" (n=58) and patients with "high-probability PA" (n=59), defined as having any of the following: computed tomography-confirmed adrenal adenoma plus lateralizing adrenal vein sampling (AVS) without surgery, high ARR and hypokalemia but nonlateralizing AVS, or ARR more than four times the upper limit of normal. The PRA 95th percentile was 1.0 ng/mL/h. All outliers had hypokalemia and two had adrenal adenomas. There was no difference between the confirmed and high probability groups. In the absence of highly suspicious clinical features, patients with unadjusted PRA >1.0 ng/mL/h do not warrant further investigation for PA.

NT-proBNP, a useful tool in hypertensive patients undergoing a diagnostic evaluation for primary aldosteronism

Primary aldosteronism (PA) is the most frequent form of secondary hypertension, but diagnostic tools for this disease still lack optimal accuracy. The heart is one important target tissue for damage due to excess aldosterone, and the role of natriuretic peptides is well recognized in diagnosing heart failure. We hypothesized that measuring the NT-proBNP could improve the diagnostic evaluation of PA. We enrolled 132 hypertensive patients, who underwent aldosterone to renin ratio (ARR) screening, and 81 underwent an intravenous saline loading test (ivSLT) because of a high ARR. The NT-proBNP level positively correlated with the ARR and inversely correlated with the renin level. The NT-proBNP level was higher in patients with a high ARR than in those with a low ARR and higher in patients with a positive ivSLT than in those with a negative ivSLT. After logistic regression analysis, an NT-proBNP value above the median and male gender were predictors of a positive ivSLT. The proportion of patients with a positive ivSLT ranged from only 23 % in females with a low NT-proBNP to 93 % in males with a high NT-proBNP. NT-proBNP and gender are predictors of a positive PA confirmatory test. These findings highlight the possibility of using NT-proBNP to identify which patients with a high ARR should receive a complete PA diagnostic evaluation.

A High Aldosterone to Renin Ratio Is Associated With High Serum Parathyroid Hormone Concentrations in the General Population

Activation of the renin-angiotensin-aldosterone system (RAAS) is associated with high serum PTH concentrations and vice versa. The aim of this study was to analyze the associations of the plasma aldosterone concentration (PAC), the plasma renin concentration (PRC), or the aldosterone to renin ratio (ARR) with serum PTH concentrations in a sample from the general population of northeast Germany. We selected 3105 subjects (25-88 y) from the first 5-year follow-up examination of the Study of Health in Pomerania. The associations of PAC, PRC, or ARR with serum PTH concentrations were examined with multivariable linear regression analyses. We further calculated adjusted mean serum PTH concentrations according to PAC, PRC, and ARR categories (≥90th and < 90th sex specific percentiles and sex specific quartiles). The models were adjusted for age, sex, estimated glomerular filtration rate, serum 25-hydroxy vitamin D concentration, waist circumference, body mass index, hypertension, diabetes mellitus, liver disease, and intake of drugs that affect the RAAS or bone metabolism. We found no associations between PAC or PRC and serum PTH concentrations in fully adjusted linear regression models. However, fully adjusted linear regression and ANOVA models revealed higher serum PTH concentrations in subjects with an ARR 90th percentile or greater than in subjects with a lower ARR. Our data show that a high ARR is associated with high serum PTH concentrations in the general population and thus add to the increasing evidence of a relation between the RAAS and PTH.

Plasma renin activity and the aldosterone-to-renin ratio are associated with the development of chronic kidney disease

The aldosterone-to-renin ratio (ARR) is used to screen for primary aldosteronism and could be an index for salt sensitivity. The association between ARR and the development of chronic kidney disease (CKD) is completely unknown. A longitudinal observational study involving 689 participants from a general Japanese population (mean age 58.2 years; 68.5% women) who did not have CKD and were not receiving antihypertensive medication at baseline was conducted. The estimated glomerular filtration rate (eGFR) was calculated from serum creatinine levels, and CKD was defined as eGFR less than 60 ml/min per 1.73 m(2) and/or dipstick-positive proteinuria. The associations of baseline plasma renin activity (PRA), plasma aldosterone concentration, and ARR with the development of CKD were examined using Cox proportional hazard regression analysis adjusted for sex, age, BMI, smoking, drinking, history of hypercholesterolemia, diabetes mellitus, and cardiovascular disease, SBP, and baseline eGFR. During a mean 9.1-year follow-up, 118 participants developed CKD. A 1 standard deviation increment in the natural log-transformed (ln) ARR was positively associated with the incidence of CKD (hazard ratio 1.29, P = 0.012). LnPRA showed an inverse association (hazard ratio 0.76, P = 0.007). Meanwhile, plasma aldosterone concentration was not associated with CKD. Individuals who developed CKD had significantly lower baseline PRA (0.97 vs. 1.14 ng/ml per h; P = 0.03) and higher baseline ARR levels [66.6 vs. 56.8 (pg/ml)/(ng/ml per h); P = 0.02] than those who did not. Lower PRA and higher ARR were associated with the development of CKD in a general population, suggesting that they are independent predictors of CKD.

Aldosterone-to-Renin Ratio as a Predictor of Stroke Under Conditions of High Sodium Intake: The Ohasama Study

Aldosterone is thought to have deleterious effects on the cardiovascular system. The aldosterone-to-renin ratio (ARR) is more reproducible than aldosterone levels alone and could be an index for inappropriate aldosterone secretion or activity. We previously reported the apparent relation between ARR and hypertension in subjects with high sodium intake. This prospective study investigated the risk of ARR for a first stroke in a general population stratified by sodium intake. We obtained plasma renin activity (PRA) and plasma aldosterone concentrations (PAC) for 883 participants aged ≥ 35 years not receiving antihypertensive treatment in the general population of Ohasama (mean age: 59.0 ± 11.3 years; 65.6% women). Over a mean of 10.9 follow-up years, 45 strokes occurred. The median PRA, PAC, and ARR were 1.2 ng/ml/h, 6.4 ng/dl, and 5.3 ng/dl per ng/ml/h, respectively. Using Cox regression, we computed hazard ratios adjusted for sex, age, body mass index (BMI), and systolic blood pressure. No association between logARR and stroke was observed in subjects overall. However, in subjects with high sodium intake (≥ median of 4,058 mg/day (salt equivalent, 10.5 g/day)), each 1 s.d. increase in logARR was associated with an increased hazard ratio for stroke (hazard ratio: 1.49, P = 0.04). No significant association was observed in subjects with low sodium intake (P = 0.7). When we repeated all the analyses using logPRA or logPAC, no significant associations were found. These results suggest that high ARR, that is, relative aldosterone excess, is a predictor for stroke under conditions of high sodium intake.

Aldosterone-to-renin ratio and nocturnal blood pressure decline in a general population

Aldosterone-to-renin ratio (ARR) is an index for inappropriate aldosterone activity and salt sensitivity. We previously reported that elevated ARR might be associated with salt-sensitive hypertension. Because salt-sensitive hypertensive patients are reported to show a diminished nocturnal decline in blood pressure, we hypothesized that high ARR may be associated with diminished nocturnal decline in blood pressure (generally referred to as a 'nondipping' pattern), especially in individuals with high sodium intake. This study tested this hypothesis in 184 participants aged at least 55 years not receiving antihypertensive treatment in a general Japanese population (age: 67.6 ± 6.9 years; 71.7% women). Ambulatory blood pressure monitoring identified 63 (34.2%) participants with a nondipping pattern (nocturnal decline of SBP <10%). The median plasma renin activity (PRA), plasma aldosterone concentration (PAC), and ARR were 0.8 ng/ml per h, 8.3 ng/dl, and 8.7 ng/dl per (ng/ml per h), respectively. After adjustment for possible confounding factors, each 1 SD increase in logARR was associated with the prevalence of nondipping pattern (odds ratio, 1.95; P = 0.002). This association was observed in individuals in the highest tertile of 24-h urinary sodium excretion estimated from spot urine data (e24-hUNa; ≥179.6 mEq/day; P = 0.01) but disappeared in those in the lowest tertile of e24-hUNa (<147.9 mEq/day; P = 0.6). In those in the highest tertile of e24-hUNa, PRA was significantly lower in nondippers than in dippers (0.49 vs. 0.85 ng/ml per h) despite no differences in PAC. These results suggest that relative aldosterone excess might be related to a nondipping pattern of blood pressure, especially in individuals with high sodium intake.

Plasma aldosterone levels and aldosterone-to-renin ratios are associated with endothelial dysfunction in young to middle-aged subjects

ObjectiveSmall clinical studies suggested a role for aldosterone in the development of endothelial dysfunction. We investigated whether the plasma aldosterone concentration (PAC) or the aldosterone-to-renin ratio (ARR) were associated with decreased endothelial function as measured by flow-mediated dilation (FMD) of the brachial artery in the general population. MethodsOur study population comprised 972 participants from the Study of Health in Pomerania, who were not treated with antihypertensive medication. We performed age-stratified (<50 and ≥50 years) ordinal logistic regression analyses. FMD was categorised as decreased (1st quintile), moderate (2nd–4th quintile), or increased (5th quintile). PAC and ARR were divided into low, moderate, and high values according to age- and sex-specific tertiles. All models were re-calculated for 871 subjects with PAC and ARR within the study-specific reference ranges. Odds ratios (OR) and 95% confidence intervals (CI) are presented. ResultsSubjects <50 years with high PAC (OR 1.60; 95% CI 1.07–2.38) or ARR (OR 1.81; 95% CI 1.21–2.73) had higher odds for decreased FMD than subjects with low PAC or ARR, respectively. Similar results were obtained in analyses restricted to subjects with PAC and ARR within the reference range. High-normal PAC (OR 1.62; 95% CI 1.07–2.47) or ARR (OR 1.62; 95% CI 1.05–2.50) was associated with higher odds for decreased FMD when compared with low-normal PAC or ARR, respectively. These associations were not observed in subjects ≥50 years. ConclusionsHigh and high-normal PAC or ARR contribute to an impaired FMD and subsequently the progression of subclinical atherosclerosis in young to middle-aged subjects.

Antihypertensive efficacy of spironolactone: what about sex?

We read with interest the paper of Parthasarathy et al. [1], investigating the blood pressure (BP) response to two different diuretics [a mineralocorticoid receptor antagonist (MRA) and a thiazide diuretic] in patients subdivided, according to aldosterone-to-renin ratio (ARR) value, in high and low ARR group, respectively. Given the high incidence of primary aldosteronism and the widely recognized adverse effects of aldosterone on cardiovascular system, further research on MRA use in hypertensive patients is warranted.